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O35240

- ASIC3_RAT

UniProt

O35240 - ASIC3_RAT

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Protein
Acid-sensing ion channel 3
Gene
Asic3, Accn3, Drasic
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei26 – 261Potassium ion selectivity and permeability

GO - Molecular functioni

  1. PDZ domain binding Source: RGD
  2. enterobactin transporter activity Source: Ensembl
  3. ligand-gated sodium channel activity Source: MGI
  4. protein binding Source: IntAct
Complete GO annotation...

GO - Biological processi

  1. detection of chemical stimulus involved in sensory perception of pain Source: Ensembl
  2. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  3. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
  4. response to acid Source: Ensembl
  5. response to acidity Source: MGI
  6. response to heat Source: Ensembl
  7. sodium ion transmembrane transport Source: GOC
  8. sodium ion transport Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiREACT_198302. Stimuli-sensing channels.

Protein family/group databases

TCDBi1.A.6.1.2. the epithelial na(+) channel (enac) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 3
Short name:
ASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Dorsal root ASIC
Short name:
DRASIC
Gene namesi
Name:Asic3
Synonyms:Accn3, Drasic
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 4

Organism-specific databases

RGDi708578. Asic3.

Subcellular locationi

Cytoplasm By similarity. Cell membrane; Multi-pass membrane protein By similarity
Note: In part cytoplasmic in cochlea cells By similarity. Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei20 – 4021Helical; Reviewed prediction
Add
BLAST
Topological domaini41 – 435395Extracellular Reviewed prediction
Add
BLAST
Transmembranei436 – 45621Helical; Reviewed prediction
Add
BLAST
Topological domaini457 – 53377Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi20 – 201V → P: No effect on selectivity or channel function. 1 Publication
Mutagenesisi21 – 211F → S: Loss of channel function. 1 Publication
Mutagenesisi26 – 261T → K: Alters selectivity of the channel for sodium. No effect on channel function. 1 Publication
Mutagenesisi40 – 401T → G: Loss of regulation by PKC through PRKCABP; when associated with G-523. 1 Publication
Mutagenesisi523 – 5231S → G: Loss of regulation by PKC through PRKCABP; when associated with G-40. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 533533Acid-sensing ion channel 3
PRO_0000181303Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei40 – 401Phosphothreonine; by PKC Inferred
Disulfide bondi93 ↔ 187 By similarity
Disulfide bondi165 ↔ 172 By similarity
Glycosylationi176 – 1761N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi283 ↔ 372 By similarity
Disulfide bondi317 ↔ 368 By similarity
Disulfide bondi321 ↔ 366 By similarity
Disulfide bondi330 ↔ 352 By similarity
Disulfide bondi332 ↔ 344 By similarity
Glycosylationi400 – 4001N-linked (GlcNAc...) Reviewed prediction
Modified residuei523 – 5231Phosphoserine; by PKC Inferred

Post-translational modificationi

Phosphorylated by PKA By similarity. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiO35240.

PTM databases

PhosphoSiteiO35240.

Expressioni

Tissue specificityi

Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal chord and brain stem.4 Publications

Developmental stagei

Expression is first detected at E15.5. Strongly expressed perinatally.1 Publication

Inductioni

Transcriptionally regulated by the proinflamatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs.6 Publications

Gene expression databases

GenevestigatoriO35240.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with LIN7B, MAGI1 and GOPC By similarity. Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
InadlQ63ZW7-32EBI-982374,EBI-8158524From a different organism.
Slc9a3r1Q9JJ195EBI-982374,EBI-982391
Slc9a3r2Q920G22EBI-982374,EBI-982439
StomP541163EBI-982374,EBI-8004826From a different organism.

Protein-protein interaction databases

DIPiDIP-35759N.
IntActiO35240. 4 interactions.
MINTiMINT-1777886.
STRINGi10116.ENSRNOP00000011300.

Structurei

3D structure databases

ProteinModelPortaliO35240.
SMRiO35240. Positions 41-464.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi530 – 5334PDZ-binding By similarity

Domaini

The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1 By similarity.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00640000091217.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiO35240.
KOiK04830.
OMAiTECHMEC.
OrthoDBiEOG72VH5P.
PhylomeDBiO35240.
TreeFamiTF330663.

Family and domain databases

InterProiIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERiPTHR11690. PTHR11690. 1 hit.
PfamiPF00858. ASC. 1 hit.
[Graphical view]
PRINTSiPR01078. AMINACHANNEL.
TIGRFAMsiTIGR00859. ENaC. 1 hit.
PROSITEiPS01206. ASC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35240-1 [UniParc]FASTAAdd to Basket

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MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV    50
LLSLAAFLYQ VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR 100
SRLTPNDLHW AGTALLGLDP AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL 150
YARAGHSLED MLLDCRYRGQ PCGPENFTVI FTRMGQCYTF NSGAHGAELL 200
TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV QIHSQDEPPA 250
IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP 300
LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK 350
DCASPALDAM LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN 400
RSESYITENV LVLDIFFEAL NYEAVEQKAA YEVSELLGDI GGQMGLFIGA 450
SLLTILEILD YLCEVFQDRV LGYFWNRRSA QKRSGNTLLQ EELNGHRTHV 500
PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL 533
Length:533
Mass (Da):59,227
Last modified:January 1, 1998 - v1
Checksum:i294B57322C74B3DC
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF013598 mRNA. Translation: AAB69328.1.
RefSeqiNP_775158.1. NM_173135.1.
UniGeneiRn.24225.

Genome annotation databases

EnsembliENSRNOT00000011300; ENSRNOP00000011300; ENSRNOG00000008380.
GeneIDi286920.
KEGGirno:286920.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF013598 mRNA. Translation: AAB69328.1 .
RefSeqi NP_775158.1. NM_173135.1.
UniGenei Rn.24225.

3D structure databases

ProteinModelPortali O35240.
SMRi O35240. Positions 41-464.
ModBasei Search...

Protein-protein interaction databases

DIPi DIP-35759N.
IntActi O35240. 4 interactions.
MINTi MINT-1777886.
STRINGi 10116.ENSRNOP00000011300.

Chemistry

BindingDBi O35240.
ChEMBLi CHEMBL5757.

Protein family/group databases

TCDBi 1.A.6.1.2. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSitei O35240.

Proteomic databases

PRIDEi O35240.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000011300 ; ENSRNOP00000011300 ; ENSRNOG00000008380 .
GeneIDi 286920.
KEGGi rno:286920.

Organism-specific databases

CTDi 9311.
RGDi 708578. Asic3.

Phylogenomic databases

eggNOGi NOG262945.
GeneTreei ENSGT00640000091217.
HOGENOMi HOG000247010.
HOVERGENi HBG004150.
InParanoidi O35240.
KOi K04830.
OMAi TECHMEC.
OrthoDBi EOG72VH5P.
PhylomeDBi O35240.
TreeFami TF330663.

Enzyme and pathway databases

Reactomei REACT_198302. Stimuli-sensing channels.

Miscellaneous databases

NextBioi 625060.
PROi O35240.

Gene expression databases

Genevestigatori O35240.

Family and domain databases

InterProi IPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view ]
PANTHERi PTHR11690. PTHR11690. 1 hit.
Pfami PF00858. ASC. 1 hit.
[Graphical view ]
PRINTSi PR01078. AMINACHANNEL.
TIGRFAMsi TIGR00859. ENaC. 1 hit.
PROSITEi PS01206. ASC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons."
    Waldmann R., Bassilana F., de Weille J.R., Champigny G., Heurteaux C., Lazdunski M.
    J. Biol. Chem. 272:20975-20978(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. "A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells."
    Lingueglia E., de Weille J.R., Bassilana F., Heurteaux C., Sakai H., Waldmann R., Lazdunski M.
    J. Biol. Chem. 272:29778-29783(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ASIC1.
    Strain: Wistar.
    Tissue: Brain.
  3. Cited for: TISSUE SPECIFICITY.
  4. "The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore."
    Coscoy S., de Weille J.R., Lingueglia E., Lazdunski M.
    J. Biol. Chem. 274:10129-10132(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF VAL-20; PHE-21 AND THR-26.
  5. "Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+."
    Babinski K., Catarsi S., Biagini G., Seguela P.
    J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  6. "Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors."
    Voilley N., de Weille J.R., Mamet J., Lazdunski M.
    J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, INHIBITION BY DRUGS.
  7. "Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons."
    Immke D.C., McCleskey E.W.
    Nat. Neurosci. 4:869-870(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY LACTATE, FUNCTION.
  8. "Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF."
    Catarsi S., Babinski K., Seguela P.
    Neuropharmacology 41:592-600(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY NPFF.
  9. "Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons."
    Sutherland S.P., Benson C.J., Adelman J.P., McCleskey E.W.
    Proc. Natl. Acad. Sci. U.S.A. 98:711-716(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels."
    Mamet J., Baron A., Lazdunski M., Voilley N.
    J. Neurosci. 22:10662-10670(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  11. "Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system."
    Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.
    Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  12. "How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons."
    Mamet J., Lazdunski M., Voilley N.
    J. Biol. Chem. 278:48907-48913(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, INDUCTION BY NGFB.
  13. "Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade."
    Immke D.C., McCleskey E.W.
    Neuron 37:75-84(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY LACTATE AND CALCIUM.
  14. "Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability."
    Deval E., Baron A., Lingueglia E., Mazarguil H., Zajac J.-M., Lazdunski M.
    Neuropharmacology 44:662-671(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. "A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons."
    Diochot S., Baron A., Rash L.D., Deval E., Escoubas P., Scarzello S., Salinas M., Lazdunski M.
    EMBO J. 23:1516-1525(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION BY APETX2 TOXIN.
  16. "ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1."
    Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M.
    J. Biol. Chem. 279:19531-19539(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF THR-40 AND SER-523, PHOSPHORYLATION AT THR-40 AND SER-523.
  17. "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current."
    Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.
    J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DLG4, SUBCELLULAR LOCATION.
  18. Cited for: FUNCTION, INTERACTION WITH STOM, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiASIC3_RAT
AccessioniPrimary (citable) accession number: O35240
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: January 1, 1998
Last modified: September 3, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Potentiated by FMRFamide-related neuropeptides By similarity. Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi